Clinical trials

The SHIELD trial is a single-center, randomized, controlled, parallel-group, single-blinded clinical trial investigating whether performing RIPC one day before surgery-compared to not performing RIPC-reduces postoperative neuronal injury, as reflected by the maximum serum NfL concentration within the first 2 postoperative days, in non-cardiac surgery patients at risk for postoperative delirium.

The PROST-BP trial is a prospective, single-center, randomized, patient-blinded, non-inferiority trial investigating whether intermittent oscillometric blood pressure monitoring is non-inferior to continuous intraarterial blood pressure monitoring in reducing intraoperative hypotension in patients having robot-assisted radical prostatectomy.

Study Rationale: Previous in vitro and retrospective in vivo studies suggest that optimal linezolid concentrations (between 2 and 7 mg/L) achieve clinical efficacy and microbiological eradication while minimizing side effects like thrombocytopenia and the emergence of resistance. No prospective or randomized clinical trial has confirmed these findings, and there is no consensus on how to adjust linezolid dosing to achieve optimal drug concentrations. Objectives: The primary objective is to determine if model-informed precision dosing optimizes linezolid dosing to achieve therapeutic trough concentrations compared to a standard dose. Secondary objectives include assessing the PK/PD profile, investigating the prevalence of linezolid resistance among gram-positive bacteria, assessing microbiological resolution of infection, and evaluating the safety and tolerability of linezolid. Methodology: This study is an open, monocentric pilot randomized controlled trial with two arms: standard dose therapy versus dose adjustment based on model-informed precision dosing using therapeutic drug monitoring and PK/PD targets developed in TMDx software. Sample Size: 28 patients, 14 in each group. Assumptions are based on only 25% of patients in intensive care achieving the optimal therapeutic range with standard dosing, compared to an expected 80% achieving this with model-informed precision dosing. Selection Criteria: Adult patients (18+ years) already starting linezolid treatment for gram-positive infections, expected to require treatment beyond the next calendar day. Exclusions include imminent death, expected or confirmed pregnancy, expected linezolid treatment of less than 4 days or more than 4 weeks. Outcomes: The primary endpoint is defined as the difference in the proportion of patients in the intervention and in the control groups who maintained a trough linezolid concentration of 2 to 7 mg/L on Day 7 and Day 13.